Children at risk despite malaria treatment

Repeated bouts of malaria may leave children vulnerable to other deadly infections and even cardiovascular disease later in life. Now, a new study may explain why.

About 200 children in Blantyre, Malawi, took part in the study. It compares kids in one group, who have mild or the more serious cerebral malaria, to those in another group, who are healthy. Malaria is caused by the bite of an infected mosquito that transmits parasites first to the liver and then to red blood cells. Tests showed the blood vessels of the two groups of children were different – especially those with cerebral malaria.

It has to do with inflammation. It’s long been known that diseases that cause acute fevers – febrile diseases – trigger inflammation in the endothelium. That’s the smooth, thin layer of cells lining blood vessels throughout the body.

“What people hadn’t looked at was whether that resolves after you give treatment and after the fact that the febrile illness goes away,” said Dr. Chris Moxon.

Moxon is the lead author of the study and a clinical lecturer at Liverpool University. At the time of the study he was a PhD Fellow at Wellcome Trust. He says when healthy, the endothelium allows the blood to flow unrestricted, similar to Teflon coating on a non-stick cooking pan.

“We were just thinking that the burden of malaria is extremely high in Africa – in the sort of level that’s very difficult for people who haven’t lived in a malaria endemic country to understand. Children are getting sometimes, in highly endemic areas, more than one infective bite a day and many repeated infections. And we just wondered what that might do to children and their endothelium in the long term,” he said.

Moxon and his colleagues knew that mosquito control programs appeared to have effects far beyond reducing malaria cases.

He said, “There have been a number of studies that have shown in small areas if you reduce or eliminate malaria that the reduction in mortality is higher than you might expect from simply a reduction in the number of acute febrile illnesses. So we wondered whether there was another effect that malaria was having. Whether this might be that the endothelium remained activated for a longer period of time.”

By an activated endothelium, he means inflamed. There are blood tests to determine if that’s the case.

“The endothelial cells have proteins on the surface that give the endothelial cells a lot of their function. And these proteins are shed in healthy individuals, but when you get an illness and the endothelium changes they’re shed at higher levels. So you can measure these proteins in the blood and malaria changes the blood vessels. It sort of hijacks the endothelium to be able to stick to blood vessels. And that’s a sort of mechanism that the parasite uses to prevent going through the spleen and stop being cleared by our immune system,” he said.

So, if the endothelium is activated or inflamed, how does that predispose a child to other infections and possible future cardiovascular disease?

Moxon said, “If the endothelium is activated it may become more permeable. So it may become more leaky. For example, that may allow viruses or bacteria to leak and invade areas, for example, in the gut. And then cardiovascular disease, those processes of inflammation make the endothelium more leaky to allow fat to accumulate inside the blood vessel wall.”

There’s been greater awareness in recent years of inflammation’s role in a host of diseases. While more study is needed, Moxon says controlling inflammation may help in preventing other infections following bouts with malaria -- and in turn reduce child mortality. He says statins – drugs used to lower cholesterol – may be one possibility. The drugs have been shown to help reduce inflammation.